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In the November 2011 issue of Scientific American, author Bijal Trivedi looks at the ongoing controversies surrounding the use of genetically modified mosquitoes to fight dengue fever. We asked biologist Mark Q. Benedict and Helen Wallace, the director of GeneWatch UK, to illuminate the issues surrounding the release of genetically modified insects into the wild.

Current technologies we use against mosquitoes simply are not adequate: existing measures are losing the war. The choice of implementing GM mosquitoes is not a choice of no risk versus risk, it is a matter of choosing the least risky among all existing choices in a war against very real continuing disease risk. More »

The release of genetically modified (GM) insects should follow a precautionary approach, because what appears well understood in the lab can have unintended consequences when released on a large scale into the environment. On release, GM mosquitoes become part of a complex system involving predators and prey, other mosquito species, four types of dengue virus, other tropical diseases transmitted by mosquitoes, and the humans—including children—who are being bitten and infected. More »

Genetically Modified Mosquitoes Could Be an Important Tool in the Fight against Disease

By Mark Q. Benedict

Readers of Scientific American will appreciate the high failure rate of what seem to be promising innovations. The much ballyhooed "Ginger" was going to change the world and the way our cities are built. Hadn't multitudes of celebrities gushed over Ginger and invested? I could not wait to find out what something given such a sexy code name could be. A new energy source? A new concept for a computing interface? A self-healing material? You may have shared my disappointment when the mysterious Ginger turned out to be a rather clunky, unattractive but easily operated scooter named the Segway. My initial response that Ginger was not going to change the world has thus far been correct. Segways have indeed created a niche populated by policemen and tourists, and it has stimulated the production of other cheaper vehicles that are used in much the same way. They were not the game-changer that was anticipated. I guess I'll wait for Mary Ann.

I was also among those who hopefully (and skeptically) followed cold fusion in 1989. Against the original claims, however, excess heat was not measured in subsequent experiments. The claims didn't hold up. Yes, there are still folks pursuing the idea, and I would be the last to discourage them. The world could use endless clean energy in such a concentrated form.

We can safely say that controlling mosquito populations by releasing genetically modified (GM) mosquitoes is not another cold fusion of innovation, but it may be a Ginger. For the sake of those who need help, I hope not.

Current technologies we use against mosquitoes simply are not adequate: existing measures are losing the war. None are easy and even fewer are affordable for vulnerable individuals and governments charged with mosquito control. They do not fully protect, and their use entails direct risks to human health and the environment. So the choice of implementing GM mosquitoes is not a choice of no risk versus risk, it is a matter of choosing the least risky among all existing choices in a war against very real continuing disease risk.

Genetically modified mosquitoes are not the only innovative solution being tested in this war: resistance-proof insecticides, anti-mosquito fungi, bioprospecting for drugs and repellents, biopesticides, better education programs and new traps are in play. There is room for all of these, but all of these entail risks, not least of which is diversion of limited resources to little effect.

In this context, we must consider whether releasing sexually sterile GM mosquitoes is safe. History says "yes." Sterile insects have been safely used for decades. Target pests have never become established due to failure of sterility, and sterile insects are often used to prevent the establishment of insects where they do not occur. The sterile mosquito technology is being tested specifically because it is the safest possible means to begin to explore their potential. It is difficult to argue that use of the most common measure—nonspecific insecticides—is a more desirable option.

Novel technologies are always in the midst of a withering process that subjects them to the brutal stresses of real-world trials, and implementation of genetically modified mosquitoes will fly or fail based quite simply on whether they work. And by "work," I include their effects on the environment and acceptability by those at risk. Picking winners among all the options is impossible. We simply know too little of their possibilities or the future to predict their success in myriad disease transmission settings.

Regulatory structures are important controls on the implementation of innovation. They guide safe use and fair testing. As the feature indicates, these are coalescing contemporaneously with the development of genetically modified mosquitoes, but they are not being developed in a vacuum. New guidelines largely reflect ethical and safe practices that are already widely acknowledged and codified. Any effort to release genetically modified mosquitoes without proper considerations for such existing law, ethics and safety imperils the entire field, so motivation among those conducting trials to stay above board is high. The community developing GM mosquito technology is always looking over its shoulder at the India experience (in 1974, scientists studying the genetic modification of insects for disease control were accused of conducting secret biowarfare research) and is in no mood to repeat it.

Just as the world is a beautiful mosaic of cultures, it is a mosaic of attitudes toward, and regulation of, genetically modified organisms. This is a natural outgrowth of perspectives toward the natural world, the role of science and even religious beliefs. Therefore, regulation will differ as determined by law and treaty of sovereign countries. Whereas many countries will adopt similar standards rather than developing them de novo, the variety of perspectives dictates that in respect for others we must accept a variety of regulatory solutions. Similarly, community engagement must fit the affected people. What may be sufficient engagement for my community (which is accustomed to eating GM foods and having GM crops planted in fields we see every day) may not fit yours. This is natural and should be welcomed.

GM mosquito technology must be evaluated as a complement to existing control measures. Will it entail the risks that some fear? This should be carefully determined in small trials. Will it be too expensive? That is for those considering it to assess based on experience, their economies and the effects of release. Will it cause environmental damage that can be avoided with other technologies? Let's find out, one cautious small step at a time and in comparison with all the alternatives. But there is no scientific basis for the assertion that sterile insect technology will get out of control and should not be tested.

Although I am among those with hopes that GM mosquitoes will improve human health with minimal environmental effects, it is simply too soon to tell. Because there is no well-financed advocacy machine to push them against demand, GM mosquitoes will have to stand on their own merits in the real world of human diseases. That is the battle which they deserve a chance to fight.

Mark Q. Benedict is currently a Marie Curie Fellow at the University of Perugia, Italy. His professional activities include developing technology for genetic control of mosquitoes, biosafety guidelines and mosquito mass production equipment and facilities. He obtained his PhD and BS at the University of Florida.

The release of genetically modified (GM) insects should follow a precautionary approach, because what appears well understood in the lab can have unintended consequences when released on a large scale into the environment. On release, GM mosquitoes become part of a complex system involving predators and prey, other mosquito species, four types of dengue virus, other tropical diseases transmitted by mosquitoes, and the humans—including children—who are being bitten and infected.

An expert report (pdf) to the European Food Safety Authority lists a wide variety of issues that should be addressed prior to the deliberate release of any GM insects. They include the adverse effects associated with the flow of genes into the wild population; the interactions of the GM insect with target and nontarget organisms; the impact on agricultural management practices and on management measures to control insects that are vectors for diseases; and a variety of potential effects on human health. The latter include allergies and irritation; the presence of live female mosquitoes; potential changes in the ability of mosquitoes to transmit disease; and accidental ingestion (including of larvae and eggs). Other issues that have been raised elsewhere include: the potential for viruses to evolve into more virulent forms; the impacts on human immunity and hence cases of disease; whether other species of mosquito (transmitting the same or different diseases) might occupy the ecological niche vacated by a falling population of the target species (pdf); and whether infection with dengue has a protective effect against yellow fever.

The first open releases of GM mosquitoes have now taken place in the Cayman Islands, Malaysia and Brazil. In all three countries the biotechnology company Oxitec released GM Aedes aegypti mosquitoes (yellow fever mosquitoes) with the intention of reducing the population of this species, which also transmits dengue fever. In choosing the British Overseas Territory of the Cayman Islands to undertake the first releases, Oxitec bypassed the provisions of the Cartagena Protocol (covering impacts on biodiversity) and the Aarhus Convention (covering access to environmental information), both of which would apply in the U.K. The Cayman trials were in an inhabited area where dengue is not endemic; the smaller Malaysian trial was in an uninhabited area in a country where dengue is endemic; and the ongoing, much larger Brazilian trials are in an inhabited area where dengue is endemic. Only in Malaysia did the company openly consult the public, and even there, a small-scale release caused public concerns due to the lack of transparency about the timing and insufficient public information. Further, only a summary of the risk assessment has been published, leaving the regulator's decisions about what hazards to include, and whether or not they were significant, open to dispute.

Although no doubt genuine in its desire to tackle dengue fever, Oxitec is a commercial company with a patented technology to sell (pdf). Its business plan relies on convincing the governments of dengue endemic countries to pay for ongoing releases of its GM mosquitoes to maintain suppression of the mosquito population. Its investors include the University of Oxford, the venture capital company Oxford Capital Partners (which offers significant tax breaks to its investors), and a Boston-based multimillionaire (pdf). The former U.K. science minister, Lord Drayson, and the former president of the Royal Society, Lord May, have both acted as advisors to investors in the company. Oxitec has also received significant U.K. government subsidy via the Biotechnology and Biological Sciences Research Council as well as the Technology Strategy Board. Its open-release experiment in Malaysia was funded via a translational grant from the Wellcome Trust. Although the company is a spin-off from Oxford, the university's ethics board plays no role in overseeing its experiments.

Research on public attitudes to potential releases of GM mosquitoes to tackle malaria in Mali found that participants wanted to see evidence that GM mosquitoes could reduce malaria without adverse effects on human health and the environment, and many were skeptical that the technology would work. A majority of participants would support a release that satisfied their conditions, but a substantial minority would not support a release under any circumstances. Whereas it is difficult to extrapolate from a small study in a single country (which included mainly male participants), the study does succeed in raising some important issues. How is people's consent to be obtained for such experiments, given that most people would only grant it if certain conditions were fulfilled? And, is it ethical to undertake experiments if some people continue to oppose them?

Oxitec seems to have treated this ethical problem as largely an issue of public relations. In Cayman it released a video claiming its GM mosquitoes were sterile, rather than explaining that they breed and the offspring die as pupae; it also didn't mention that they were genetically modified. In Brazil activities have included attending carnival dressed up as mosquitoes. Concerns that the technology is not 100 percent effective, leaving some female (biting) mosquitoes to breed, have simply been ignored.

For observers, it is hard to understand how decades of debate at the World Health Organization and elsewhere have come to this. Is there really any regulatory oversight; any data required of any company; and any ethical requirements before GM insects can be released into the open? Decisions appear to be being taken by a small circle of powerful investors who have decided they must rush to commercialize a particular technology, rather than in consultation with the people who will be affected. Who is going to be liable if anything goes wrong? And will any problems be reversible as releases happen on an ever larger scale?

Helen Wallace is the director of GeneWatch UK. She has worked as an environmental scientist in academia and industry and as senior scientist at Greenpeace UK, where she was responsible for science and policy work on a range of issues. She has a degree in physics from the University of Bristol and a PhD in applied mathematics from University of Exeter